Efficacy and Safety of HS-25 or in Combination With Atorvastatin in Chinese Adults With Primary Hypercholesterolemia (HS-25-C-01)

Multi-center,Randomized,Double Blind, Double Dummy,Placebo Controlled, Efficacy and Safety Study of HS-25 in Combination With Atovastatin in Adults With Primary Hypercholesterolemia

To determine the efficacy of the HS-25 (10mg or 20mg) or in combination with Atorvastatin (10mg)in reducing low density lipoprotein-cholesterol (LDL-C) levels after a 12-week period of treatment in adults with primary hypercholesterolemia; To determine the safety of HS-25 (10mg or 20mg) or in combination with Atorvastatin (10mg)in subjects with LDL-C after a 40-week period of treament.

Study Overview

• Status: Unknown
• Conditions: Primary Hypercholesterolemia
• Intervention / Treatment: Drug: HS-25 10mg; Drug: Placebe of HS-25 and Atorvastatin; Drug: HS-25 20mg; Drug: HS-25 10mg combination with Atorvastatin; Drug: Atorvastatin 10mg; Drug: HS-25 20mg combination with Atorvastatin

Detailed Description

This is a 12-week, randomized, double-blind, double dummy, placebo-controlled study designed to assess the effects of the cholesterol absorption inhibitor HS-25 (10mg or 20mg) or in combination with Atorvastatin (10mg) on LDL-C levels in adults who have untreated LDL-C levels ranging from 3.36-4.88mmol/L(130-189 mg/dL)and fasting triglyceride levels < 350 mg/dL. Eligibility is restricted to 18-70 years old men or women who are using a highly effective birth control method or are not of childbearing potential;subjects with not treated by statins in six months before signature of the informed consent.Subjects with diabetes, a history of myocardial infarction or other clinical evidence of atherosclerotic vascular disease or treated are not eligible for participation in the study.

• Study Type: Interventional
• Enrollment (Anticipated): 720
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects who are 18 to 70 years of age, male or female using a highly effective birth control method or not of child-bearing potential, at Visit 1 (screening visit);
• LDL-C 3.36mmol/L (130 mg/dL) to 4.88 mmol/L (189 mg/dL) (inclusive) on a cholesterol lowering diet but no lipid modifying drug treatment (statins) for at least 6 weeks before signed written informed consent;
• A qualifying LDL-C value must be obtained at the beginning and end of the placebo run-in (Visit 2 and Visit 3) and the Visit 3 value must be within 12% of the value at Visit 2, higher or lower; the average of both qualifying values must be in the range of 3.36mmol/L (130 mg/dL) to 4.88 mmol/L (189 mg/dL) (inclusive) for inclusion in the study.

Exclusion Criteria:

• Liver transaminases > 1.5 x upper limit of normal.
• Homozygous Familial Hypercholesterolemia.
• Subject who was diagnosed as diabetes with aged greater than 40 years old.
• Subject who was diagnosed as diabetes with one of the following of cardiovascular risk factorss: Hypertention Bp ≥ 140/90mmHg,or smoking, or low HDL-C (1.04mmol/L), or BMI≥28kg/m2.
• Women who are pregnant or breast feeding.
• Atherosclerotic cardiovascular disease including Arteriosclerotic heart disease, Acute coronary syndrome，Coronary artery bypass graft,Coronary angioplastyPeripheral arteriosclerosis,Cerebrovascular accident - history of Severe Endiocrine disease (for example Thyroid function abnormal) - History of a positive test for human immunodeficiency virus, hepatitis B or hepatitis C.
• History of advanced cancer - Arrhythmias need to be treated by medications
• Had severe injured or surgery in 6 months before study start.
• Hypersensitive to HS-25 or place.
• History of intolerance to ezetimibe.
• Participation other studies in three months.
• Treatment with a fibric acid derivative (eg, fenofibrate, gemfibrozil), probucol, warfarin, systemic corticosteroid, cyclosporine or other immunosuppressant agent within the prior 12 weeks.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HS-25 10mg; HS-25 10mg, Placebo of HS-25 1 tablet, Placebo of Aorvastatin 1 tablet, oral once daily, 12weeks	Drug: HS-25 10mg; HS-25 10mg 1tablet add placebo of HS-25 1 tablet, placebo of Atorvastatin 1 tablet; Drug: Placebe of HS-25 and Atorvastatin; Placebe of HS-25 2 tablets, Placebo of Atorvastatin 1 tablets
Experimental: HS-25 20mg; HS-25 10mg 2 tablets, Placebo of Aorvastatin 1 tablet, oral once daily, 12weeks	Drug: Placebe of HS-25 and Atorvastatin; Placebe of HS-25 2 tablets, Placebo of Atorvastatin 1 tablets; Drug: HS-25 20mg; HS-25 10mg 2 tablets, placebo of Atorvastatin 1 tablet
Experimental: HS-25 10mg combination with Atorvastatin; HS-25 10mg, Aorvastatin 10mg, Placebo of HS-25 1 tablet, oral once daily, 12 weeks	Drug: Placebe of HS-25 and Atorvastatin; Placebe of HS-25 2 tablets, Placebo of Atorvastatin 1 tablets; Drug: HS-25 10mg combination with Atorvastatin; HS-25 10mg 1 tablet , Atorvastatin 10mg 1 tablet, Placebo of HS-25 1 tablet; Drug: Atorvastatin 10mg; Atorvastatin 10mg 1 tablet, placebo of HS-25 2 tablets
Experimental: HS-25 20mg combination with Atorvastatin; HS-25 20mg, Aorvastatin 10mg, oral once daily, 12 weeks	Drug: Atorvastatin 10mg; Atorvastatin 10mg 1 tablet, placebo of HS-25 2 tablets; Drug: HS-25 20mg combination with Atorvastatin; HS-25 10mg 2 tablets, Atorvastatin 10mg 1 tablet
Active Comparator: Aorvastatin 10mg; Aorvastatin 10mg, Placebo of HS-25 2 tablets, oral once daily, 12 weeks	Drug: Placebe of HS-25 and Atorvastatin; Placebe of HS-25 2 tablets, Placebo of Atorvastatin 1 tablets; Drug: Atorvastatin 10mg; Atorvastatin 10mg 1 tablet, placebo of HS-25 2 tablets
Placebo Comparator: Placebo of HS-25 and Aorvastatin; Placebo of HS-25 2 tablets, Placebo of Aorvastatin 1 tablet, oral once daily, 12 weeks	Drug: Placebe of HS-25 and Atorvastatin; Placebe of HS-25 2 tablets, Placebo of Atorvastatin 1 tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent change of LDL-C	Percent change in LDL-C from baseline to week 12 for each group	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent change of LDL-C	Percent change in LDL-C from baseline to week 2, 4, 8, 18, 24, 38, 52 for each group	52 weeks ( including 2, 4, 8, 18, 24, 38, 52 weeks)
Percent change of Non-HDL-C	Percent change in Non-HDL-C from baseline to week 2, 4, 8, 12, 18, 24, 38, 52 for each group	52 weeks ( including 2, 4, 8, 12, 18, 24, 38, 52 weeks)
Percent change of HDL-C	Percent change in HDL-C from baseline to week 2, 4, 8, 12, 18, 24, 38, 52 for each group	52 weeks ( including 2, 4, 8, 12, 18, 24, 38, 52 weeks)
Percent change of TC, TG, Apo B, Apo Al	Percent change in TC, TG, Apo B, Apo Al from baseline to week 2, 4, 8, 12, 18, 24, 38, 52 for each group	52 weeks ( including 2, 4, 8, 12, 18, 24, 38, 52 weeks)

Collaborators and Investigators

• Sponsor: Zhejiang Hisun Pharmaceutical Co. Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2015
• Primary Completion (Anticipated): December 28, 2018
• Study Completion (Anticipated): May 28, 2019

Study Registration Dates

• First Submitted: February 7, 2018
• First Submitted That Met QC Criteria: March 7, 2018
• First Posted (Actual): March 14, 2018

Study Record Updates

• Last Update Posted (Actual): October 18, 2018
• Last Update Submitted That Met QC Criteria: October 17, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin
• Other Study ID Numbers: HS-25-C-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No